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ENDOCRINE
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CLASSICAL ALGORHYTHM• PITUITARY
– ANTERIOR– POSTERIOR
• THYROID• PARATHYROID• PANCREAS (endo.)• ADRENAL
– CORTEX– MEDULLA
• DEGENERATION (aka, “involution”)
• INFLAMMATION• NEOPLASM
– BENIGN– MALIGNANT
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BETTER ALGORHYTHM• NON-NEOPLASTIC
– HYPER-function– HYPO-function
• NEOPLASTIC– FUNCTIONAL– NON-FUNCTIONAL– Functional endocrine
malignancies are RARE. Why?
• PITUITARY– ANTERIOR– POSTERIOR
• THYROID• PARATHYROID• PANCREAS (endo.)• ADRENAL
– CORTEX– MEDULLA
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FEEDBACK SYSTEMS• HYPOTHALAMUS • ANTERIOR PITUITARY • ENDOCRINE GLAND • END ORGAN • HYPOTHALAMUS
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HORMONES• POLYPEPTIDE (2nd
MESSENGER)• STEROID (DIRECT on
NUCLEUS)
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ACIDOPHILS
BASOPHILS
CHROMOPHOBES
AXONS
AXONS and “PITUI-”cytes
A
I P www.freelivedoctor.com
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ANTERIOR PITUITARY• ACIDOPHILS
–GROWTH HORMONE–PROLACTIN
• BASOPHILS–TSH–ACTH–LH, FSH
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POSTERIOR PITUITARY
• OXYTOCIN (contracts uterine smooth muscle)
• VASOPRESSIN (ADH) (vasoconstriction, gluconeogenesis, platelet aggregation, release of Factor-VIII and vWb factor, concentrates urine, main effects on kidney and brain)
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PITUITARY PATHOLOGY• CLINICAL FEATURES, mimic the endocrine effects or mass
effects)
• FUNCTIONING ADENOMAS
• HYPO-PITUITARISM
• POSTERIOR PITUITARY SYNDROMES
• HYPOTHALAMIC (SUPRASELLAR) TUMORS
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CLINICAL FEATURES• HYPER: growth, lactation, thyroid,
adrenal cortex
• HYPO: growth, thyroid, adrenal cortex
• MASS EFFECT: visual fields, brain
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G
A
L
A
C
T
O
R
R
H
E
A
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GIGANTISM
(excess somatotropin [GH] BEFOREepiphyseal
closure)
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ACROMEGALY:
(excess somatotropin
[GH] AFTER epiphyseal closure)
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MOON FACIES
BUFFALO HUMP
STRIAE
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Normal pituitary.
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HYPO-pituitarism• Pituitary tumors, functional or not.• NON-pituitary tumors, primary or metastatic• Pituitary surgery, of course• Radiation, of course• “Apoplexy”, i.e., sudden hemorrhage• Sheehan’s syndrome (Post-partum ischemic
necrosis)• Cysts (Rathke’s cleft)• Empty sella syndrome, (is NOT a disease)• Genetic defects (pit-1 gene mutations)
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POSTERIOR pituitary• DIABETES INSIPIDUS• SIADH (Syndrome of Inappropriate Andi- Diuretic Hormone)
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DIABETES INSIPIDUS• ADH deficiency• Head trauma, tumors, inflam.
hypothal/pit• Hyperdiureses with LOW sp.gr.
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Inappropriate ADH• ADH EXCESS
– Hyponatremia, cerebral edema, neurologic symptoms
– Neoplasms, esp. Small Cell CA.– NON-neoplastic lung diseases– Posterior pituitary injury
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15-25 grams
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thyroid,
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HYPER-THYROIDISM• aka, thyrotoxicosis• Diffuse• Nodular• Adenoma• Carcinoma• Neonatal• Secondary to TSH pituitary adenoma
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HYPER-THYROIDISM• HYPERMETABOLISM• Tachycardia, palpitations• Increased T3, T4• Goiter• Exophthalmos• Tremor• GI hypermotility• Thyroid “storm”, life threatening
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HYPO-THYROIDISM• 1° Developmental• 1° Surgery, I-131, external radiation• 1° Auto-immune (i.e., Hashimoto’s)• 1° Iodine deficiency• 1° Li+, iodides, p-aminosalicylates• 2° (pituitary)• 3° (hypothalamic, rare)
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HYPO-THYROIDISM
• Cretinism– Severe retardation– CNS/Musc-skel– Short stature– Protruding tongue– Umbilical hernia
• Myxedema (coma)– Sluggishness– Cool skin
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THYROIDITIS• Hashimoto (Auto-Immune) (Lymphoid follicles with
germinal centers), MOST COMMON cause of acquired hypothyroidism in USA
• Subacute Granulomatous (DeQuervain)
• Subacute Lymphocytic (just like Hashimoto’s but NO fibrosis and no germinal centers), often post-partum
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GRAVES DISEASE(aka, diffuse toxic goiter)
• HYPERTHYROIDISM• EXOPHTHALMOS• PRE-TIBIAL MYXEDEMA
• Autoimmune, auto-antibodies to TSH
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SCALLOPING
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GRAVES DISEASE(aka, diffuse toxic goiter)
PLUMMER DISEASE(aka, nodular toxic goiter)
HARDER TO TREAT
Surg
PTU (Propyl Thio Uracil)
I-131
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GOITERS(aka, thyromegaly, diffuse or nodular)
• IODINE deficiency• Increased TSH• Goitrogens, e.g., cabbage, Brussels sprouts,
cauliflower, turnips, cassava)• Associated with HYPO thyroidism eventually, NOT
hyperthyroidism
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GOITER
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Thyroid Neoplasms
• “Nodules” vs. true neoplasms
• Adenomas vs. Carcinomas
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“NODULES”• Solitary vs. Multiple• Younger vs. Older• Male vs. Female• Hx. neck radiation vs. NO Rx.• “Cold” vs. HOT (really NOT-cold)
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NEOPLASMS• ADENOMAS
– FOLLICULAR–HÜRTHLE
(oxyphilic)
• CARCINOMAS– FOLLICULAR–PAPILLARY– MEDULLARY (AMYLOID)– ANAPLASTIC (worst)
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HÜRTHLE CELL ADENOMA, note “atypia”www.freelivedoctor.com
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ORPHAN ANNIE CELLS in PAPILLARY CARCINOMAwww.freelivedoctor.com
MEDULLARY CARCINOMA of the thyroid with “HYALINIZATION”, i.e.,
AMYLOID!!! www.freelivedoctor.com
HYALINIZATION showing APPLE GREEN birefringence in CONGO RED stain, i.e., AMYLOID
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BIOLOGIC BEHAVIOR
• Papillary CA lymph nodes
• Follicular CA blood vessels, bone
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35-40 mgwww.freelivedoctor.com
PTH• HYPOCALCEMIA is MAIN STIMULUS
(9-10.5 mg/dl)
• ANTAGONIZES CALCITONIN
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PARATHYROID DISORDERS• HYPER-
– PRIMARY (usually adenomas)– SECONDARY (LOW CA++ of Renal Failure)
• HYPO-: Surgical, congenital, familial, idiopathic
• PSEUDO-HYPO-– (end organ resistance)
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HYPER-PARATHYROIDISM
• Bone pain, fractures• Nephrolithiasis• Constipation, ulcers, gallstones• Depression, lethargy• Weakness, fatigue• Valve calcifications
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HYPO-PARATHYROIDISM• Neuromuscular irritability• Mental status change• Parkinsonism like effects• Lens calcification* (paradox)• Widened QT interval• Defective, carious, teeth
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ADRENAL CORTEX• Glomerulosa (Salt), mineralocorticoids
– ALDOSTERONE
• Fasciculata (Sugar), glucocorticoids– CORTISOL
• Reticularis (Sex), gonadocorticoids– ANDROGENS, ESTROGENS
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4 g.www.freelivedoctor.com
HYPERADRENALISM• HYPERALDOSTERONISM• CUSHING SYNDROME
(CORTISOL)• ADRENOGENITAL (VIRILIZING)
SYNDROME
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CUSHING SYNDROME
• CENTRAL OBESITY• MOON FACIES• WEAKNESS• HIRSUTISM• HYPERTENSION• DIABETES• OSTEOPOROSIS• STRIAE
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CUSHING SYNDROME
• PITUITARY ACTH INCREASE• TUMOR ACTH INCREASE• HYPERPLASIA OF CORTEX• ADENOMA OF CORTEX• CARCINOMA OF CORTEX
• EXOGENOUS STEROIDS (90%)
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PRIMARY HYPERALDOSTERONISM(Conn’s Syndrome)
Na+ RETENTIONK+ EXCRETIONHYPERTENSION
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PRIMARY HYPERALDOSTERONISM
• CORTICAL NEOPLASM• CORTICAL HYPERPLASIA• FAMILIAL (rare)
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SECONDARY HYPERALDOSTERONISM
• DECREASED RENAL PERFUSION
• EDEMA (HEART, LIVER, KIDNEY)
• PREGNANCY
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ADRENOGENITAL SYNDROME
• VIRILIZATION/feminization• CORTICAL NEOPLASM• CORTICAL HYPERPLASIA• 21-Hydroxylase Deficiency
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ADRENAL INSUFFICIENCY
• PRIMARY ACUTE (ADRENAL CRISIS)
• PRIMARY CHRONIC (ADDISON DISEASE)
• SECONDARY (PITUITARY)
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PRIMARY ACUTE• RAPID WITHDRAWAL OF STEROIDS• MASSIVE ADRENAL HOMORRHAGE
(WATERHOUSE-FRIDERICHSEN, if it follows infection and shock)– Newborns with DIFFICULT DELIVERY– ANTICOAGULANT RX– POSTSURGICAL DIC PATIENTS
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PRIMARY CHRONIC• Most of Addison disease is auto-immune
adrenalitis• INFECTIONS• METASTASES• GENETIC DISORDERS
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NEOPLASMS• ADENOMAS of ADRENAL CORTEX
• CARCINOMAS of ADRENAL CORTEX
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ADRENAL MEDULLA• PHEOCHROMOCYTOMAS, aka, primary
tumors of the adrenal medulla– 10% arise in an MEN setting– 10% are EXTRA-adrenal– 10% are bilateral– 10% are malignant– 10% are in childhood– You can only call them malignant if they
metastasize
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PHEOwww.freelivedoctor.com
TWO crucially important points specific for endocrine tumors:
• 1. FUNCTIONING carcinomas are very RARE in ANY endocrine gland. Why? (KEY principle of oncology)
• 2. Benign adenomas may have extremely bizarre nuclei, but are most usually BENIGN!!!
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MEN-1, aka, Wermer Syndrome (3 P’s)
• HYPERPARATHYROIDISM, chiefly hyperplasia
• Pancreatic endocrine tumors• Pituitary adenoma, usually
prolactinoma
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MEN-2• MEN-2A (SIPPLE): Pheo, Medullary CA.,
Parathyroid hyperplasia• MEN-2B: NO hyperparathyroidism, but
neuromas present• Familial Medullary Thyroid CA
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PINEAL “GLAND”
• PINEALOMAS–PINEOBLASTOMAS–PINEOCYTOMAS
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ENDOCRINE
PANCREAS
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Exocrine
Endocrine
Islets
Alpha Cells
Beta Cells
Delta Cells (suppress insulin and glucagon)
Pancreatic Polypeptide (PP) cells
Epsilon Cells make
gherlin
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DIABETES MELLITUS
• 16 Million in the USA• 1 Million/yr• 50K people die of it per year
in the USA
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How to Diagnose Dm:• Glucose >200• Or…………….• Fasting glucose >126 trice• Or…………….• Post-prandial glucose > 200, 2 hrs
AFTER standard OGTT (Oral Glucose Tolerance Test)
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TWO Types of DM• 1• Genetic• Autoimmune• Childhood (juvenile)
onset• Antibodies to beta cells• Beta cell depletion• NON-OBESE patients
• 2• Genetic, but diff. from
Type 1• NOT autoimmune• Adult, or maturity
onset, e.g., 40’s, 50’s• Insulin may be low,
BUT, peripheral resistance to insulin is the main factor
• OBESE patients
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INSULIN• FAT
– IN-creased glucose uptake– IN-creased lipogenesis– DE-creased lipolysis
• MUSCLE– IN-creased glucose uptake– IN-creased glycogen synthesis– IN-creased protein synthesis
• LIVER– DE-creased gluconeogenesis– IN-creased glycogen synthesis– IN-creased lipogenesis
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PATHOGENESIS• 1• T-Lymphocytes
reacting against poorly defined beta cell antigens
• Inflammatory inflitrate, chronic, i.e., “INSULITIS”
• 2• Diet• Life Style• Obesity• INSULIN RESISTANCE• Beta cells UN-able to
adapt to the “long term demands of insulin resistance”
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MODY (Maturity Onset Diabetes of the Young)
• Multiple types• 2-5% of diabetics• Primary beta cell defects• Multiple genetic mechanisms,
especially GLUCOKINASE mutations
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PANCREAS in Dm
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PANCREAS in Dm
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COMPLICATIONS• MACRO-VASCULAR disease, i.e., ASCVD• MICRO-VASCULAR disease, kidneys, retina,
nerves• IMMUNE related problems, INFECTIONS, e.g.,
TB, pneumonia, pyelonephritis, candida, etc.
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COMPLICATIONS• ADVANCED GLYCATION
– collagen, laminin, polypeptides, GBM (glomerular basement membrane)
• ACTIVATION of PROTEIN KINASE C, VEGF, endothelin-1, increased ECM, decreased fibrinolysis, inflam. cytokines
• INTRACELLULAR HYPERGLYCEMIA
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COMPLICATIONSMORPHOLOGY
• (MACRO-vascular) Atherosclerosis• MICRO-vascular
– Retinopathy– Nephropathy- glomerular, vascular, KW– Neuropathy
• Infections
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ATHEROSCLEROSIS
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ATHEROSCLEROSIS
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RETINOPATHY in DmShows microaneurysms, areas of hemorrhage, cotton wool spots, hard exudates, venous beading, neovascularization, retinal detachment, vitreous detachment, pre retinal hemorrhage
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NEPHROPATHYKimmelstiel-Wilson (KW) Kidneys
Is…………
“Nodular” glomerulosclerosis
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NEPHROPATHYNEPHROSCLEROSIS
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NEPHROPATHYGBM thickening
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NEPHROPATHYDiffuse
Mesangial
Sclerosis
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INFECTIONS in Dm• SKIN• TUBERCULOSIS• PNEUMONIA• PYELONEPHRITIS• CANDIDA
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NEOPLASMS of the Endocrine Pancreas
• Islet cell tumors– Beta cells INSULINOMAS (NOT rare)– Alpha cells GLUCAGONOMAS (rare)– Delta cells SOMATOSTATINOMAS (rare)– GASTRINOMAS, producing ZOLLINGER-
ELLISON SYNDROME, consisting of increased acid and ulcers
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